Melatonin effects on the left ventricular function in neonates with persistent pulmonary hypertension

The aim of this study is to investigate the effects of melatonin on the left ventricular (LV) function in persistent pulmonary hypertension of the newborn (PPHN) and to assess its potential role in enhancing cardiac performance and reducing oxidative stress. This randomized controlled trial was conducted on 80 neonates (≥ 36 weeks' gestational age) with PPHN confirmed by echocardiography (Echo). Participants were assigned to receive standard therapy alone or in combination with oral melatonin. LV function was evaluated using echocardiographic parameters, and levels of serum biomarkers of oxidative stress and inflammation were also measured. Unlike the placebo group, the melatonin group exhibited significantly better LV function, regarding the conventional and advanced echocardiographic parameters. Additionally, melatonin administration was associated with earlier weaning from mechanical ventilation (MV) and respiratory support, shorter hospital stays, lower levels of serum high-mobility group box-1 (HMGB1) protein, and N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Melatonin can enhance LV function in PPHN, likely through its cardioprotective and antioxidative mechanisms. These findings support melatonin as a promising adjunctive therapy in neonatal pulmonary hypertension, warranting further investigation in larger clinical trials.

registered on ClinicalTrials.gov (ID: NCT07090720), URL: https://clinicaltrials.gov/study/NCT07090720?cond=NCT07090720&rank=1 , Date: (29/7/2025).

• PPHN induces hypoxic respiratory failure, jeopardizing multiorgan function, including LV performance. • Oxidative stress is crucial in pulmonary arterial hypertension development.

• Melatonin's antioxidant and vasodilatory properties may serve as an adjunctive therapy in PPHN and enhance myocardial protection from the hypoxic effect of PPHN.